1. Field of the Invention
The present invention relates generally to cardiac pacemakers, and more particularly to an exercise-responsive implantable cardiac pacemaker in which the stimulation rate is adaptively regulated according to the blood temperature of the pacemaker patient.
2. Prior Art
In situations where the natural pacemaker or pacing system of a patient's heart is disturbed because of age, disease or injury, it is customary to employ artificial pacing of the heart by implanting a cardiac pacemaker. In an atrial-triggered pacemaker, the P-wave generated preceding atrial contraction is detected to initiate the delivery of a pacing stimulus to the ventricle. It has been found that an atrial-triggered pacemaker is, to an extent, responsive to physical exertion of the patient, unlike the conventional fixed-rate pacemaker. However, in many cardiac patients, such as those suffering from atrial flutter, fibrillation, or sick-sinus syndrome, P-wave generation is not responsive to physiological conditions. Hence, the exercise-responsive advantage of atrial triggered pacemakers is not available to such patients.
In the past, many proposals have been advanced for adapting the pacemaker stimulation rate to patient exercise using a detected biological signal. Biological parameters proposed as suited for exercise-responsive adjustment of pacing rate include, for example, the pH value of the venous blood, the central venous oxygen saturation, the respiration rate, the Q-T interval (i.e., the interval from ventricular depolarization to repolarization), and the central venous blood temperature.
Cardiac pacemakers using the respiration rate or the Q-T interval for pacing rate control are currently in development and/or undergoing clinical testing. However, the use of the Q-T interval can easily cause oscillations, and thus, pacemaker-triggered tachycardia. Furthermore, the parameter these devices employ for rate control makes them particularly subject to disruption by medications currently in use to act on the electrolyte or membrane metabolism, such as beta-blocking agents, diuretics, antiarrhythmics, and digitalis.
As pointed out in patent No. OS 26 09 365 of the Federal Republic of Germany, dated Sept. 8, 1977, the central venous blood temperature may serve as a biological parameter for controlling or regulating the stimulation rate of a rate-adjustable cardiac pacemaker. A temperature-controlled pacemaker as described in that patent has not, to my knowledge, heretofore been used in actual practice. It does not offer the advantage of employing a relatively small and simple temperature sensor that may be incorporated in the catheter lead in proximity to the pacing electrode. The aforementioned publication proposes that the stimulation rate be adjusted in parallel with the blood temperature; that is to say, a rise in blood temperature would provide a correspondingly higher stimulation rate, not excluding a linear dependency between the two in an exemplary partial range of from 37.degree. to 39.degree. C.
A similar rate-adaptive pacemaker which depends on central venous blood temperature has been proposed in U.S. Pat. No. 4,436,092. According to the latter, a particular exercise algorithm is set forth, based on an observed mathematical relationship between blood temperature and heart rate in a normally functioning heart under stress, employing constants derived from experimental data obtained on the specific patient. The designated algorithm is utilized in conjunction with a signal obtained using a thermistor which is positioned in the patient's heart in a manner simiar to that of the German Pat. No. 26 09 305, to control the pulse frequency of the pacemaker's pulse generator. This type of control is not materially different from the control principle proposed in the German Pat. No. 26 09 305, and neither of these approaches provides true physiological adaptation of stimulation rate according to the condition of physical exertion or lack of exertion of the cardiac pacemaker patient. For example, the system proposed in the aforementioned U.S. Pat. No. 4,436,092 while not altogether clear, provides only a single algorithmic relationship between stimulation rate and instantaneous blood temperature. In U.S. Pat. No. 4,543,954, the same patentees of the U.S. Pat. No. 4,436,092 again propose a unitary algorithm relating heart rate to blood temperature, but in which the control algorithm produces abrupt jumps between two or three discrete stimulation rates for rest and exercise, depending on the sign of the derivative of temperature with respect to time relative to designated set points. Here again, the pacemaker operation does not result in stimulation of the heart in a manner corresponding to the normal physiological response.
3. U.S. Pat. No. 4,688,573
The invention disclosed in my aforementioned application Ser. No. 747,111, now U.S. Pat. No. 4,688,573 ("the '573 patent") provides a temperature-driven rate-responsive cardiac pacemaker implemented to distinguish between the physiologically determined changes of blood temperature occurring when the patient is in a resting state and those occurring when the patient is undergoing physical exertion, and to adaptively vary the stimulation rate based on change in blood temperature but according to either of two distinct and different relationships the selection of which depends on whether or not the temperature change is attributable to exercise.
My experimental data involving a multiplicity of healthy persons led me to conclude that changes in the blood temperature and in the heart rate of the individual undergoing physical stress exhibit substantially parallel behavior, independent of the individual's short-term working capacity. Therefore, rate-responsive cardiac pacing based on the blood temperature should fulfull the following conditions:
1. a definite correlation between blood temperature and heart rate, which may be assumed to be substantially linear; and
2. an intra-individual reproducibility of this correlation, since the ratio of blood temperature to heart rate appears to a large extent to be independent of the individual's working capacity.
The blood temperature is readily and consistently measured with long-term precision using known high sensitivity temperature sensors, such as thermistors or semiconductor chip thermistors. A temperature sensor has the further advantages of being of extremely small size and low energy dissipation, making it well suited for incorporation into the lead or electrode assembly of an implantable cardiac pacemaker.
Changes in blood temperature during periods when the individual is inactive, occurring, for example, with fever, ovulation, or during the normal circadian cycle, are accompanied by changes in heart rate in normally healthy persons as well as in pacemaker patients. The correlation between changes in blood temperature and heart rate in the resting state of an individual is different from that existing when the individual is undergoing physical stress.
The invention disclosed in the '573 patent, in one aspect, recognizes the problem of differentiating between physiologically determined changes of blood temperature occurring during states of rest and physical exercise of the individual; and that a solution to the problem is needed to achieve adequate adaptation of the pacing rate with change of blood temperature according to whichever of those states is at hand. The solution permits the stimulation rate to be adapted to the particular physiological condition of the pacemaker patient.
According to an important feature of the invention disclosed in the '573 patent, the cardiac pacemaker employs means for distinguishing between a rise in the individual's blood temperature owing, say, to the normal stress of his walking up a flight of stairs and that owing to the onset of fever. More particularly, there is an evaluation of the nature of the increase (or decrease) in blood temperature over a predetermined time interval to determine its physiological origin, and a consequent selective adjustment of the pacing rate based on instantaneous blood temperature according to whether the origin lies in exercise or in the normal changes that may occur during a state of rest. According to an embodiment of that invention, this is achieved in part using a field of characteristic curves, each of which is representative of the normal dependence of heart rate on blood temperature for a specified physiological condition, storing the set of curves in a matrix memory, and controlling the stimulation rate based on blood temperature according to the correlation therebetween exhibited by the curve(s) selected in response to the determination of the attributable physiological condition.
According to a preferred embodiment of the invention described in the '573 patent, a single basic characteristic curve (hereinafter called the "basic curve" or "resting curve") is selected as representative of the correlation between changes in absolute blood temperature and heart rate within a selected range under substantially any physiological condition in which physical stress is not a determining factor. Such a curve is representative, then, of the temperature change attributable, for example, to fever or to the normal circadian cycle. A typical example of circadian rhythm-based change is the decrease in blood temperature and heart rate accompanying sleep. While blood temperature change (increase or decrease) of about 0.5.degree. C. occurs at night, and such change is also observed with exercise, the nightime changes occur slowly compared with the exercise changes.
The preferred embodiment of the '573 patent further employs a set of characteristic curves which correlate changes of blood temperature and heart rate within the aforementioned selected range under conditions of physical stress (these curves hereinafter called "exercise curves"). The exercise curves are individually selected for controlling the stimulation rate (in switching from control according to the basic curve) when the rate of change of blood temperature over a preset time interval exceeds a predetermined value. For example, selection of an exercise curve for pacing rate control may be based on an increase of at least 0.04.degree. C. per minute in the patient's blood temperature.
Thus, if the cardiac pacemaker is functioning according to the basic curve, a measurement of absolute blood temperature along that curve corresponds to a distinct heart rate, and the stimulation rate of the pacemaker is controlled accordingly. For example, a heart rate of about 70 beats per minute (bpm) will typically accompany a central venous blood temperature of 37.degree. C., while an elevated heart rate of, say, 95 bpm will accompany a fever temperature of 38.5.degree. C. In both cases, the cardiac pacemaker patient is in a resting condition, which is identifiable by the absence of a time rate of change of his blood temperature in excess of the predetermined value. Hence, the stimulation rate remains under the control of the basic curve, close to the rate also observed in healthy persons.
If the patient now physically exerts himself, his blood temperature will increase per unit time at a rate significantly higher than any increase which might normally occur in the resting state during the same time interval. If that time rate of change exceeds the predetermined value (which is selected to be commensurate with any condition of exercise), the cardiac pacemaker thereupon switches functioning modes from the basic curve to the applicable exercise curve, such that the stimulation rate is regulated according to the latter curve. Since blood temperature increases with the amount of physical exercise by the individual patient, the pacing rate, controlled by temperature increase, will also increase according to the extent of exercise.
When the patient ceases the physical exertion his blood temperature will drop, which produces an adjustment of the stimulation rate of the pacemaker in the form of a decrease according to the respective exercise curve. The pacemaker continues to function in this manner until the decrease of blood temperature per unit time reaches a predetermined lower limit indicative of more gradual change or no further significant change. At that point, the reduced rate of change of blood temperature with time is indicative of the patient being in a resting state, and the pacemaker's temperature-driven rate-responsive function commences a return to the basic curve in a manner avoiding any abrupt change in the patient's heart rate.
According to another aspect of the invention disclosed in the '573 patent, a period of time is selected as a further criterion for predetermining the point at which the pacemaker's stimulation rate adjustment function changes from control according to an exercise curve to that of the basic curve. This period may, for example, range from a few minutes to an hour. In any case, it should be chosen to reflect a time interval following which, if no significant variation has occurred in the rate of change of the patient's blood temperature, it is appropriate to return to reliance on the basic curve for stimulation rate control. In the preferred embodiment of that invention, this period is chosen to have a duration of thirty minutes. These criteria serve to place a limit on the incidence of any pacemaker-mediated tachycardia. Of course, if the patient if actually undergoing physical stress for a longer time, there will continue to be a significant relative change in measured temperature per preselected time interval (that is, rate of change of blood temperature with time), and accordingly the adjustment of pacing rate will continue to be controlled according to the exercise curve.
If the patient is subjected to consecutive intervals of increasing and decreasing physical stress over a relatively long period, as might occur, for example, in the course of a long walk or light hike, it is possible ultimately to achieve a metabolic state of balance (i.e., equilibrium, or a steady state), where heat production equals heat loss, and in which the pacemaker follows the different metabolic conditions over a lengthy time interval with the respective adequate new rate. According to a further aspect of the invention disclosed in the '573 patent, logic circuitry of the cardiac pacemaker is implemented to recognize the existence of such a steadystate condition, and should it continue over the entire duration of the aforementioned selected period--say, thirty minutes--to use this as a criterion for returning control of the pacing rate to the basic curve. The pacemaker circuitry is arranged to initiate a program of transition by which the pacing rate is reduced in a physiologically appropriate manner.
It follows that in the case of a long-lasting exercise, cardiac output may decrease with this reduction in stimulation rate. However, if the patient continues to undergo physical stress, with the continuing heat production his body will react with a new increase in blood temperature. This is caused by the more limited ability to dissipate the same amount of heat by maintaining the same blood skin circulation with lower heart rate, if the decrease in pacing rate leads to a lower cardiac output. Consequently, the pacemaker rate adjustment control will revert again from the basic curve to the applicable exercise curve, following this new increase in blood temperature. On the other hand, if the patient's blood temperature does not undergo significant rate of change with time after reaching the steady-state condition, the adjustment of pacing rate will continue in accordance with the basic curve.
The course (i.e., rate of change, or slope) of each of the characteristic curves may be freely selected, provided that this slope is adapted to the physiological conditions of the pacemaker patient. In particular, the curves may be linear, with the slope of the exercise curve set, for example, from 40 to 120 bpm per degree Centigrade, and the slope of the resting curve set, for example, from 5 to 25 bpm per degree Centrigrade. For most cardiac pacemaker patients, the slope is most appropriately set or near the midpoint of these exemplary ranges, viz., 80 bpm/.degree.C. for exercise and pb 15 pk bpm/.degree.C. for rest. At the higher end of the blood temperature range, the curves may have a decreasing slope, which better correlates to physiological conditions.
In principle, all exercise curves may be parallel to each other, for the purpose of simplifying the internal processing of the pacemaker. In that case, the adjustment of pacing rate may be carried out with only a basic curve and the exercise curves, parallel to the abscissa, displaced according to the working point of the pacemaker.
The internal circuitry for controlling stimulation rate may be programmable as to several parameters, for the purpose of adapting the control or regulation to the particular needs of the individual patient. For example, the heart rate may be programmed for a range from 50 to 180 bpm; and the measurement range of the blood temperature may be set from 36.degree. C. to 40.degree. C. Also, periodic measurement (i.e., sampling) of blood temperature is preferred, and may be programmed to occur more rapidly with increasing rates of change of blood temperature per unit time. This assures rapid adjustment of stimulation rate commensurate with rapid changes of blood temperature of a patient undergoing physical stress, and thereby, to the physiological condition of the patient.
Experimental results indicate that intermittent, sudden fluctuations in the blood temperature sometimes occur, perhaps arising from the patient's respiration. In any event, the effect of a false indication of sudden change in blood temperature may be minimized by adjusting such a measurement to a median, maximum or minimum value.
To assure consistent measurement of blood temperature without regard to the patient's extremities involved in the physical exertion (that is, whether the arms, the legs, or both are involved), it is necessary that the temperature sensor be positioned at a site within the heart where good mixing of the venous blood occurs, such as at or near the boundary between the atrium and the ventricle. Preferably, the sensor is located from four to eight centimeters behind the electrode tip so that it will be properly situated whether the tip is positioned in the ventricle or (in consequence of looping of the lead) in the atrium.
Thus, among other things, the invention disclosed in the application Ser. No. 747,111 provides a cardiac pacemaker in which pacing rate is adaptive to changes in central venous blood temperature, by selectively controlling the pacing rate according to one or the other of at least two algorithms representing distinct non-constant relationships between heart rate and blood temperature. Further, that invention provides a temperature-driven rate-responsive cardiac pacemaker in which stimulation rate is adjusted according to any of a plurality of distinct curves relating stimulation rate to patient temperature in a non-constant manner, the specific curve for controlling the rate adjustment being selected according to a decision rule based on time rate of change of temperature, or, stated in a slightly different manner, a decision rule based at any given time on the slope of a curve that relates the time rate of change of the blood temperature to heart rate relative to a predetermined threshold value (0.04 degrees centigrade per minute in the preferred embodiment, in the case of pacing rate control being moved from the resting curve to an exercise curve).
However, circumstances may arise in which it is preferable not to use, or at least not to rely solely upon, the slope of such a curve relative to a predetermined threshold value as the decision rule (for discriminating between resting curve and exercise curve in going from the former to the latter, or the passage of a predetermined period of time without material change as the decision rule for return to the resting curve) for selectively discriminating between the two different types of curves or algorithms at any particular point in time. Accordingly, it is a principal object of the present invention to provide a rate responsive cardiac pacemaker in which central venous blood temperature of the patient in the determining parameter for adjustment of heart rate under conditions of rest and exercise according to defined algorithms, as described in the application Ser. No. 747,111, but in which a different parameter or parametric change is utilized as a criterion or discriminator for selecting between the resting and exercise algorithms.